Cardiovascular Diabetology | |
Evidence of a causal relationship between high serum adiponectin levels and increased cardiovascular mortality rate in patients with type 2 diabetes | |
Original Investigation | |
Claudia Menzaghi1  Concetta De Bonis1  Lucia Salvemini1  Lorena Ortega Moreno1  Vincenzo Trischitta2  Massimiliano Copetti3  Andrea Fontana3  | |
[1] Research Unit of Diabetes and Endocrine Diseases, IRCCS Casa Sollievo della Sofferenza, Viale Padre Pio, 71013, San Giovanni Rotondo, Italy;Research Unit of Diabetes and Endocrine Diseases, IRCCS Casa Sollievo della Sofferenza, Viale Padre Pio, 71013, San Giovanni Rotondo, Italy;Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy;Unit of Biostatistics, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy; | |
关键词: Adiponectin; ADIPOQ; Mortality; Mendelian randomization; Type 2 diabetes; | |
DOI : 10.1186/s12933-016-0339-z | |
received in 2015-11-28, accepted in 2016-01-18, 发布年份 2016 | |
来源: Springer | |
【 摘 要 】
BackgroundDespite its beneficial role on insulin resistance and atherosclerosis, adiponectin has been repeatedly reported as an independent positive predictor of cardiovascular mortality.MethodsA Mendelian randomization approach was used, in order to evaluate whether such counterintuitive association recognizes a cause-effect relationship. To this purpose, single nucleotide polymorphism rs822354 in the ADIPOQ locus which has been previously associated with serum adiponectin at genome-wide level, was used as an instrument variable. Our investigation was carried out in the Gargano Heart Study-prospective design, comprising 356 patients with type 2 diabetes, in whom both total and high molecular weight (HMW) adiponectin were measured and cardiovascular mortality was recorded (mean follow-up = 5.4 ± 2.5 years; 58 events/1922 person-year).ResultsThe A allele of rs822354 was associated with both total and HMW adiponectin [β (SE) = 0.10 (0.042), p = 0.014 and 0.17 (0.06), p = 0.003; respectively]. In a Poisson model comprising age, sex, smoking habits, BMI, HbA1c, total cholesterol, HDL-cholesterol, triglycerides, insulin therapy and hypertension, both rs822354 (IRR = 1.94, 95 % CI 1.23–3.07; p = 0.005), as well as the genetic equivalent of total adiponectin change (IRR = 1.07, 95 % CI 1.02–1.12; p = 0.003) were significantly associated with cardiovascular mortality. The observed genetic effect was significantly greater than that exerted by the genetic equivalent change of serum adiponectin (p for IRR heterogeneity = 0.012). In the above-mentioned adjusted model, very similar results were obtained when HMW, rather than total, adiponectin was used as the exposure variable of interest.ConclusionsOur data suggest that the paradoxical association between high serum adiponectin levels and increased cardiovascular mortality rate is based on a cause-effect relationship, thus pointing to an unexpected deleterious role of adiponectin action/metabolism on atherosclerotic processes.
【 授权许可】
CC BY
© Ortega Moreno et al. 2016
【 预 览 】
Files | Size | Format | View |
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RO202311104454426ZK.pdf | 949KB | download |
【 参考文献 】
- [1]
- [2]
- [3]
- [4]
- [5]
- [6]
- [7]
- [8]
- [9]
- [10]
- [11]
- [12]
- [13]
- [14]
- [15]
- [16]
- [17]
- [18]
- [19]
- [20]
- [21]
- [22]
- [23]
- [24]
- [25]
- [26]
- [27]
- [28]
- [29]
- [30]
- [31]
- [32]
- [33]
- [34]
- [35]
- [36]
- [37]
- [38]
- [39]
- [40]
- [41]
- [42]
- [43]
- [44]
- [45]
- [46]
- [47]
- [48]
- [49]
- [50]
- [51]
- [52]
- [53]
- [54]
- [55]
- [56]
- [57]